Epigenetik

Die Anaesthesiologie - Epigenetik, die Wissenschaft, die sich mit der geänderten Ablesung des Genoms ohne Veränderung der Gene selbst beschäftigt, gelangt wissenschaftlich zunehmend...     

Measured and modeled personal and environmental NO2 exposure

ABSTRACT: BACKGROUND: Measured or modeled levels of outdoor air pollution are being used as proxies for individual exposure in a growing number of epidemiological studies. We studied the accuracy of such approaches, in comparison with measured individual levels, and also combined modeled levels for each subject's workplace with the levels at their residence to investigate the influence of living and working in different places on individual exposure levels. METHODS: A GIS-based dispersion model and an emissions database were used to model concentrations of NO2 at the subject's residence. Modeled levels were then compared with measured levels of NO2. Personal exposure was also modeled based on levels of NO2 at the subject's residence in combination with levels of NO2 at their workplace during working hours. RESULTS: There was a good agreement between measured facade levels and modeled residential NO2 levels (rs = 0.8, p > 0.001); however, the agreement between measured and modeled outdoor levels and measured personal exposure was poor with overestimations at low levels and underestimation at high levels (rs = 0.5, p > 0.001 and rs = 0.4, p > 0.001) even when compensating for workplace location (rs = 0.4, p > 0.001). CONCLUSION: Modeling residential levels of NO2 proved to be a useful method of estimating facade concentrations. However, the agreement between outdoor levels (both modeled and measured) and personal exposure was, although significant, rather poor even when compensating for workplace location. These results indicate that personal exposure cannot be fully approximated by outdoor levels and that differences in personal activity patterns or household characteristics should be carefully considered when conducting exposure studies. This is an important finding that may help to correct substantial bias in epidemiological studies.     

模拟教学法可改善成人糖尿病患者的血糖控制

初级保健医师(primary care physicians,PCPs)对继续医学教育的需求很大.为了评估以病例为基础的模拟教学法是否可以提高初级保健医师对糖尿病的诊疗水平,美国明尼苏达州健康合作者研究基金会和医疗集团进行了相关的研究. 研究选择了美国明尼苏达州健康合作者研究基金会和医疗集团旗下的11个诊所的41名初级保健医师,随机分为参与模拟教学组和不参与模拟教学组.在模拟教学组中,给每位初级保健医师派发了1 2个2型糖尿病的模拟病例,这些病例都是针对研究人员在电子病历中观察到的初级保健医师诊疗水平的不足之处所专门设计的,每个模拟病例都需要初级保健医师在15分钟内完成诊疗过程.     

Immunosuppressive Effects of Opioids��Clinical Relevance

Opioid-induced immunosuppression has been demonstrated in cell culture experiments and in animal models. This is in striking contrast to the paucity of confirmatory studies in humans. This review describes the basic pharmacokinetics and –dynamics of opioid use in patients. It summarizes the major findings on opioid use and infectious complications in intensive care unit (ICU) patients, in patients with acute or chronic non-malignant pain, and in intravenous drug users (IDU). The limitations of studies in each area are discussed. For example, ethical concerns may complicate randomized placebo-controlled trials (RCT) in acute postoperative pain and for a large part of ICU patients. Importantly, most studies in patients with chronic (non-malignant) pain only inadequately report infectious complications in relation to opioid use since their incidence is usually not considered to be drug related. Infectious complications in IDUs are very frequent but cannot easily be distinguished from risk behavior or risk environment. In summary, convincing clinical evidence is lacking that opioids per se increase the rate of infectious complications in most patient categories. From a clinical standpoint, important unresolved issues are i) selection of relevant animal models, ii) opioid selection and discontinuation, and iii) the role of coexisting diseases and concomitant other medications.     

Epimutation at human chromosome 14q32.2 in a boy with a upd(14)mat-like clinical phenotype

Recently, three reports described deletions and epimutations affecting the imprinted region at chromosome 14q32.2 in individuals with a phenotype typical for maternal uniparental disomy of chromosome 14 [upd(14)mat]. In this study, we describe another patient with upd(14)mat-like phenotype including low birth weight, neonatal feeding problems, muscular hypotonia, motor and developmental delay, small hands and feet, and truncal obesity. Conventional cytogenetic analyses, fluorescence in situ hybridization subtelomere screening, multiplex ligation-dependent probe amplification analysis of common microdeletion and microduplication syndromes, and methylation analysis of SNRPN all gave normal results. Methylation analysis at 14q32.2 revealed a gross hypomethylation of the differentially methylated regions (intergenic DMR and MEG3 -DMR). Further molecular studies excluded full or segmental upd(14)mat as well as a microdeletion within this region. Evidently, the upd(14)mat-like clinical phenotype is caused by an epimutation at 14q32.2. The clinical and molecular features of this novel case are discussed with respect to the recently published cases.     

Maggot debridement therapy with Lucilia cuprina: a comparison with conventional debridement in diabetic foot ulcers

This is prospective case–control study of more than 18 months performed to assess the effectiveness of maggot debridement therapy (MDT) with the sterile larvae of Lucilia cuprina (a tropical blowfly maggot) for the treatment of diabetic foot ulcers. Literature thus far has only reported results with the temperate maggot, Lucilia sericata. This study documents outcome in diabetic foot wounds treated with maggot debridement versus those treated by conventional debridement alone. In this series of 29 patients treated with MDT, 14 wounds were healed, 11 were unhealed and 4 were classified under others. The control group treated by conventional debridement had 30 patients of which 18 wounds were healed, 11 unhealed and 1 classified under others. There was no significant difference in outcome between the two groups. The conclusion that can be made from this study is that MDT with L. cuprina is as effective as conventional debridement in the treatment of diabetic foot ulcers. It would be a feasible alternative to those at high risk for surgery or for those who refuse surgery.     

Doctor–patient concordance during HIV treatment switching decision‐making

Objectives

The aim of the study was to explore levels of doctor–patient concordance during the making of decisions regarding HIV treatment switching and stopping in relation to patient health‐related outcomes.

Methods

Adult patients attending five HIV clinics in the United Kingdom were requested to complete the study questionnaire, which included a Concordance Scale, and measures of symptoms [Memorial Symptom Assessment Short Form (MSAS) index], quality of life (EuroQol), satisfaction, adherence and sexual risk behaviour. Clinical health measures (HIV viral load and CD4 cell count) were also obtained. A total of 779 patients completed the questionnaire, giving a response rate of 86%; of these 779 patients, 430 had switched or stopped their HIV treatment and were thus eligible for inclusion. Of these patients, 217 (50.5%) fully completed the Concordance Scale.

Results

Concordance levels were high (88% scored between 30 and 40 on the scale; score range 10–40). Higher concordance was related to several patient outcomes, including: better quality of life (P=0.003), less severe and burdensome symptom experience (lower MSAS‐physical score, P=0.001; lower MSAS‐psychological score, P=0.008; lower MSAS‐global distress index score, P=0.011; fewer symptoms reported, P=0.007), higher CD4 cell count (at baseline, P=0.019, and 6–12 months later, P=0.043) and greater adherence (P=0.029).

Conclusions

High levels of doctor–patient concordance in HIV treatment decision‐making are associated with greater adherence and better physical and psychological functioning. More research is needed to establish a causal relationship between concordance and these outcomes.     

An International Reference Typing for Ch and Rg Determinants on Rare Human C4 Allotypes1

Red cells, serum and plasma samples of 20 individuals, selected for their C4 allotypes, were distributed from Bonn to five laboratories, for investigation of their Chido (Ch) and Rodgers (Rg) determinants. One anti-Ch (M.H.) and one anti-Rg(Prest.) were distributed, but the individual laboratories also used their own reagents and their own typing methods. There was general agreement in interpretation of the majority of samples. Partial inhibition for Ch and Rg was detected. Two samples gave anomalous results; one sample with C4 A1,3 BQO, QO had Ch determinants on the red cells and in plasma (partial inhibition), and another sample with C4 A3,4 B5, QO apparently lacked Ch determinants on the red cells and in plasma. Heterogeneity of anti-Ch and anti-Rg was suggested in testing red cells, perhaps, reflecting a quantitative effect. This heterogeneity was confirmed by inhibition studies. The capacity of some reagents to detect partial inhibition probably reflects qualitative as well as quantitative differences.     

Quantitative and qualitative analysis of DNA extracted from postmortem muscle tissues

Summary DNA extracted from 33 postmortem muscle specimens was analyzed using MZ 1.3, a hypervariable minisatellite probe, as well as locus-specific minisatellite probes (g3, MS1 and MS43). After storage at –25°C for 10 months, DNA from all the samples was partially (approximately 21% of total DNA) degraded even when autopsy was performed 1 day post mortem. However, more than 90% of DNA samples up to at least 3 days post mortem were suitable to obtain good restriction fragment length polymorphism (RFLP) patterns. When small strips of specimen were stored for 8 days at room temperature in moist chambers, approximately 42% of total DNA was degraded. Only 30% of these DNA samples still showed good RFLP patterns. However, no obvious relation between qualities of DNA analyzed by detection of RFLP and quantities of total and high-MW DNA became apparent. A case of familial relationship was ascertained by DNA fingerprints. Since DNA of good quality can be recovered from muscle tissues in large quantities, DNA extraction from muscle tissues and detection of RFLP patterns should be very useful for individual identification in autopsy cases.